Liposome: A Novel Aerosol Carrier of Doxophylline in Treatment of Chronic Asthma & Chronic Obstructive Pulmonary Disease

Abstract

The aim of the present research work is to develop liposomal dry powder inhaler of doxophylline by double hydration method to increase the entrapment efficiency of this hydrophilic drug. In this formulation, PVP coated mannitol and the mannitol were used as a cryoprotectant and a carrier respectively. Doxophylline, a new methylxanthine derivative, chemically designated as 7-(1,3-dixolan-2-yl-methyl) theophylline, is a more potent bronchodilator than theophylline, which is associated with a wide range of adverse effects accounting for poor compliance and high dropout rates. Powder inhaler formulation of the drug was characterized by angle of repose, compressibility index and in vitro aerosolization properties using Anderson cascade impactor including fine particle dose (212.9+ 7.2), fine particle fraction (21.69+ 1.21), % dispersibility (62.34+ 3.5) and % emission (72.1+ 0.13) at a flow rate of 28.3 lit/m for 10 seconds using 10 capsules for each determinations. The optimized formulations were subjected to stability studies at 2-8oC, RT, and 40oC for 3 months. The stability studies of LDPI were determined in terms of their visual appearance (surface characteristics and colour changes) and PDRE. The in vivo study was carried out by gamma scintigraphy and that showed better retention of doxophylline in liposomal formulation as compared to the controlled release formulation.